Conformational Change from U- to I‑Shape of Ion Transporters Facilitates K⁺ Transport across Lipid Bilayers

We have investigated, at the atomic level, the ion-fishing mechanism underlying the ion transport across membranes mediated by an artificial ion transporter composed of a hydroxyl-rich cholesterol group, a flexible alkyl chain, and a crown ether. Our results show that the transporter can spontaneously insert into the membrane and switch between the folded (U-shaped) and extended (I-shaped) conformations. The free-energy profile associated with the conformational transition indicates that compared with the U-shaped conformation of the transporter, the I-shaped one is thermodynamically more favorable. Furthermore, the free-energy profiles describing the ion translocation reveal that the transporter capturing the ion in U-shape on one side of the membrane and releasing it in I-shape on the other side constitutes a key way for the highly efficient transport of K⁺ ions. We present herewith a rigorous and rational framework to decipher the detailed ion-fishing mechanism of transmembrane ion transport with exceptionally high activity.